KR20010081116A - 트리사이클릭 파르네실 단백질 트랜스퍼라제 억제제 - Google Patents

트리사이클릭 파르네실 단백질 트랜스퍼라제 억제제 Download PDF

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Publication number: KR20010081116A
Authority: KR; South Korea
Prior art keywords: alkyl; substituted; aryl; cycloalkyl; compound
Prior art date: 1998-12-18
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

KR1020017007632A

Other languages

English (en)

Korean (ko)

Inventor

타베라스아써지.

돌로날드제이.

쿠퍼알랜비.

페레이라요한에이.

구지티모시

맬람스알랜케이.

레인디나나쓰에프.

기리자발라반비요르엠.

아폰소아드리아노

아키신씨아제이.

챠오지안핑

알바레즈카르멘

켈리죠셉엠.

랄와니타리크

데사이잭디쉬에이.

왕제임스제이.에스.

와인스타인제이

Original Assignee

둘락 노먼 씨.

쉐링 코포레이션

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-12-18

Filing date

1999-12-16

Publication date

2001-08-27

1999-12-16 Application filed by 둘락 노먼 씨., 쉐링 코포레이션 filed Critical 둘락 노먼 씨.

2001-08-27 Publication of KR20010081116A publication Critical patent/KR20010081116A/ko

Status Abandoned legal-status Critical Current

Links

239000003528 protein farnesyltransferase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 621
238000000034 method Methods 0.000 claims abstract description 196
125000000217 alkyl group Chemical group 0.000 claims abstract description 149
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 99
125000001424 substituent group Chemical group 0.000 claims abstract description 93
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 85
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 65
125000002883 imidazolyl group Chemical group 0.000 claims abstract description 25
102000004357 Transferases Human genes 0.000 claims abstract description 18
108090000992 Transferases Proteins 0.000 claims abstract description 18
150000001408 amides Chemical class 0.000 claims abstract description 15
230000002401 inhibitory effect Effects 0.000 claims abstract description 15
238000002360 preparation method Methods 0.000 claims description 234
229910052739 hydrogen Inorganic materials 0.000 claims description 111
-1 dihalo Chemical group 0.000 claims description 105
239000001257 hydrogen Substances 0.000 claims description 98
238000004519 manufacturing process Methods 0.000 claims description 91
229920006395 saturated elastomer Polymers 0.000 claims description 87
125000003118 aryl group Chemical group 0.000 claims description 85
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
229910052799 carbon Inorganic materials 0.000 claims description 47
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 44
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 43
150000002431 hydrogen Chemical class 0.000 claims description 43
125000001072 heteroaryl group Chemical group 0.000 claims description 34
229910052757 nitrogen Inorganic materials 0.000 claims description 33
210000004881 tumor cell Anatomy 0.000 claims description 32
125000005843 halogen group Chemical group 0.000 claims description 30
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 27
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
150000001721 carbon Chemical group 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 19
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 19
210000004027 cell Anatomy 0.000 claims description 16
125000001309 chloro group Chemical group Cl* 0.000 claims description 14
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
108010014186 ras Proteins Proteins 0.000 claims description 11
102000016914 ras Proteins Human genes 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
125000003107 substituted aryl group Chemical group 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
208000029742 colonic neoplasm Diseases 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
230000000711 cancerogenic effect Effects 0.000 claims description 5
231100000315 carcinogenic Toxicity 0.000 claims description 5
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
230000035772 mutation Effects 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
108090000623 proteins and genes Proteins 0.000 claims description 5
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
201000005202 lung cancer Diseases 0.000 claims description 4
208000020816 lung neoplasm Diseases 0.000 claims description 4
201000001441 melanoma Diseases 0.000 claims description 4
208000025113 myeloid leukemia Diseases 0.000 claims description 4
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
201000002528 pancreatic cancer Diseases 0.000 claims description 4
208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
108700042226 ras Genes Proteins 0.000 claims description 4
125000000547 substituted alkyl group Chemical group 0.000 claims description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
206010006187 Breast cancer Diseases 0.000 claims description 3
208000026310 Breast neoplasm Diseases 0.000 claims description 3
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
101150040459 RAS gene Proteins 0.000 claims description 2
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
239000012453 solvate Substances 0.000 claims description 2
206010005003 Bladder cancer Diseases 0.000 claims 3
208000000453 Skin Neoplasms Diseases 0.000 claims 3
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 3
239000003814 drug Substances 0.000 claims 3
210000000066 myeloid cell Anatomy 0.000 claims 3
208000023958 prostate neoplasm Diseases 0.000 claims 3
201000000849 skin cancer Diseases 0.000 claims 3
210000001685 thyroid gland Anatomy 0.000 claims 3
201000005112 urinary bladder cancer Diseases 0.000 claims 3
210000001185 bone marrow Anatomy 0.000 claims 2
230000003325 follicular Effects 0.000 claims 1
125000003106 haloaryl group Chemical group 0.000 claims 1
206010028980 Neoplasm Diseases 0.000 abstract description 9
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 9
239000004202 carbamide Substances 0.000 abstract description 5
201000011510 cancer Diseases 0.000 abstract description 4
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 abstract description 2
125000003368 amide group Chemical group 0.000 abstract 2
125000000565 sulfonamide group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 433
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 421
239000000243 solution Substances 0.000 description 269
239000000203 mixture Substances 0.000 description 185
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 183
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 139
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 134
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
239000000047 product Substances 0.000 description 130
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 122
239000000741 silica gel Substances 0.000 description 119
229910002027 silica gel Inorganic materials 0.000 description 119
239000007787 solid Substances 0.000 description 112
239000011541 reaction mixture Substances 0.000 description 110
239000003480 eluent Substances 0.000 description 76
238000003818 flash chromatography Methods 0.000 description 73
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 59
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 51
235000011114 ammonium hydroxide Nutrition 0.000 description 51
235000019439 ethyl acetate Nutrition 0.000 description 50
239000000908 ammonium hydroxide Substances 0.000 description 49
239000011734 sodium Substances 0.000 description 44
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 43
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
239000012299 nitrogen atmosphere Substances 0.000 description 40
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 38
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
238000003756 stirring Methods 0.000 description 36
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 32
238000000746 purification Methods 0.000 description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 30
238000004587 chromatography analysis Methods 0.000 description 29
239000012074 organic phase Substances 0.000 description 29
DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 26
239000012267 brine Substances 0.000 description 26
239000010410 layer Substances 0.000 description 26
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
230000008569 process Effects 0.000 description 25
150000001412 amines Chemical class 0.000 description 24
239000012044 organic layer Substances 0.000 description 24
239000012043 crude product Substances 0.000 description 23
239000003921 oil Substances 0.000 description 23
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 22
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 21
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 20
239000000706 filtrate Substances 0.000 description 20
238000010992 reflux Methods 0.000 description 20
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 18
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
238000001704 evaporation Methods 0.000 description 18
239000012300 argon atmosphere Substances 0.000 description 17
KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 17
238000001035 drying Methods 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
238000001819 mass spectrum Methods 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
238000004128 high performance liquid chromatography Methods 0.000 description 14
239000002904 solvent Substances 0.000 description 14
YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 13
XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
238000003821 enantio-separation Methods 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
150000008064 anhydrides Chemical class 0.000 description 10
150000001805 chlorine compounds Chemical class 0.000 description 10
239000012153 distilled water Substances 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 9
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 9
239000012265 solid product Substances 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 8
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical class NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
239000000284 extract Substances 0.000 description 7
238000004237 preparative chromatography Methods 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
238000005406 washing Methods 0.000 description 7
UHCZEASPZTXWPC-UHFFFAOYSA-N 2-(1-carbamoylpiperidin-4-yl)acetic acid Chemical compound NC(=O)N1CCC(CC(O)=O)CC1 UHCZEASPZTXWPC-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
229920001817 Agar Polymers 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
230000002159 abnormal effect Effects 0.000 description 6
239000008272 agar Substances 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 6
230000014759 maintenance of location Effects 0.000 description 6
150000004885 piperazines Chemical class 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000000725 suspension Substances 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 5
MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 5
PAEXAIBDCHBNDC-UHFFFAOYSA-N 2-pyridin-4-ylacetic acid Chemical compound OC(=O)CC1=CC=NC=C1 PAEXAIBDCHBNDC-UHFFFAOYSA-N 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000001246 bromo group Chemical group Br* 0.000 description 5
235000013877 carbamide Nutrition 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
238000000605 extraction Methods 0.000 description 5
239000006260 foam Substances 0.000 description 5
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PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
229960004931 histamine dihydrochloride Drugs 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
230000002390 hyperplastic effect Effects 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
QDYTUZCWBJRHKK-UHFFFAOYSA-N imidazole-4-methanol Chemical compound OCC1=CNC=N1 QDYTUZCWBJRHKK-UHFFFAOYSA-N 0.000 description 1
230000005917 in vivo anti-tumor Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
230000006122 isoprenylation Effects 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
201000005249 lung adenocarcinoma Diseases 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
XHXVAJHZTIXQQD-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-5-[(4-butoxyphenyl)methyl]-2,6-dimethylpyrimidin-4-amine Chemical compound C1=CC(OCCCC)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 XHXVAJHZTIXQQD-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
201000004931 neurofibromatosis Diseases 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000005543 phthalimide group Chemical group 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 description 1
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical group [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
239000001294 propane Substances 0.000 description 1
DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
SPSDLLKFOZNJTG-UHFFFAOYSA-N tert-butyl n-[3-(1h-imidazol-2-yl)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCC1=NC=CN1 SPSDLLKFOZNJTG-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
125000004299 tetrazol-5-yl group Chemical class [H]N1N=NC(*)=N1 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000009466 transformation Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Electroluminescent Light Sources (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

KR1020017007632A 1998-12-18 1999-12-16 트리사이클릭 파르네실 단백질 트랜스퍼라제 억제제 Abandoned KR20010081116A (ko)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US21639898A	1998-12-18	1998-12-18
US09/216,398		1998-12-18
PCT/US1999/027939 WO2000037459A1 (en)	1998-12-18	1999-12-16	Tricyclic farnesyl protein transferase inhibitors

Publications (1)

Publication Number	Publication Date
KR20010081116A true KR20010081116A (ko)	2001-08-27

Family

ID=22806914

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
KR1020017007632A Abandoned KR20010081116A (ko)	1998-12-18	1999-12-16	트리사이클릭 파르네실 단백질 트랜스퍼라제 억제제

Country Status (20)

Country	Link
EP (1)	EP1140902A1 (pt)
JP (1)	JP2002533336A (pt)
KR (1)	KR20010081116A (pt)
CN (1)	CN1326850C (pt)
AR (1)	AR021718A1 (pt)
AU (1)	AU776558B2 (pt)
BR (1)	BR9916314A (pt)
CA (1)	CA2354779A1 (pt)
CO (1)	CO5160350A1 (pt)
CZ (1)	CZ20011950A3 (pt)
HU (1)	HUP0202152A2 (pt)
IL (1)	IL143408A0 (pt)
NO (1)	NO20012961L (pt)
NZ (1)	NZ511878A (pt)
PE (1)	PE20001342A1 (pt)
PL (1)	PL348293A1 (pt)
SK (1)	SK7592001A3 (pt)
TR (1)	TR200101755T2 (pt)
WO (1)	WO2000037459A1 (pt)
ZA (1)	ZA200104233B (pt)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20160134672A (ko) *	2014-03-19	2016-11-23	비아멧 파마슈티컬즈, 인코포레이티드	2-(2,4-디플루오로페닐)-1,1-디플루오로-1-(5-치환된-피리딘-2-일)-3-(1h-테트라졸-1-일)프로판-2-올 및 이의 제조방법

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CO5160350A1 (es)	1998-12-18	2002-05-30	Schering Corp	Inhibidores de transferasa de proteina farnesilo
US7342016B2 (en)	2000-08-30	2008-03-11	Schering Corporation	Farnesyl protein transferase inhibitors as antitumor agents
WO2002056884A2 (en) *	2001-01-22	2002-07-25	Schering Corporation	Treatment of malaria with farnesyl protein transferase inhibitors
WO2002080895A2 (en) *	2001-04-06	2002-10-17	Schering Corporation	Treatment of malaria with farsenyl protein transferase inhibitors
EP1838324A2 (en)	2004-12-13	2007-10-03	Schering Corporation	Novel farnesyl protein transferase inhibitors and their use to treat cancer
CA2591123A1 (en) *	2004-12-14	2006-06-22	Schering Corporation	Farnesyl protein transferase inhibitors and methods for treating proliferative diseases
CA2637572A1 (en) *	2006-01-19	2007-07-26	Schering Corporation	Piperazine derivatives as farnesyl protein transferase inhibitors
JP6633539B2 (ja)	2014-03-19	2020-01-22	ダウアグロサイエンシィズエルエルシー	２−（２，４−ジフルオロフェニル）−１，１−ジフルオロ−１−（５−置換−ピリジン−２−イル）−３−（１ｈ−テトラゾール−１−イル）プロパン−２−オールおよびその調製工程

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL111235A (en) *	1993-10-15	2001-03-19	Schering Plough Corp	Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them
IL117798A (en) *	1995-04-07	2001-11-25	Schering Plough Corp	Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them
US5801175A (en)	1995-04-07	1998-09-01	Schering Corporation	Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5712280A (en)	1995-04-07	1998-01-27	Schering Corporation	Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
PE92098A1 (es) *	1996-07-31	1998-12-31	Schering Corp	N-cianoiminas triciclicas utiles como inhibidores de transferasa de proteina farnesilo
JP2002504144A (ja)	1997-06-17	2002-02-05	シェーリングコーポレイション	ファルネシルタンパク質トランスフェラーゼの阻害に有用なベンズピリドシクロヘプタン化合物
CO5160350A1 (es)	1998-12-18	2002-05-30	Schering Corp	Inhibidores de transferasa de proteina farnesilo

1999
- 1999-12-16 CO CO99078843A patent/CO5160350A1/es unknown
- 1999-12-16 NZ NZ511878A patent/NZ511878A/en unknown
- 1999-12-16 WO PCT/US1999/027939 patent/WO2000037459A1/en active Application Filing
- 1999-12-16 CA CA002354779A patent/CA2354779A1/en not_active Abandoned
- 1999-12-16 IL IL14340899A patent/IL143408A0/xx unknown
- 1999-12-16 CZ CZ20011950A patent/CZ20011950A3/cs unknown
- 1999-12-16 JP JP2000589531A patent/JP2002533336A/ja active Pending
- 1999-12-16 PL PL99348293A patent/PL348293A1/xx not_active Application Discontinuation
- 1999-12-16 SK SK759-2001A patent/SK7592001A3/sk unknown
- 1999-12-16 AU AU20307/00A patent/AU776558B2/en not_active Ceased
- 1999-12-16 KR KR1020017007632A patent/KR20010081116A/ko not_active Abandoned
- 1999-12-16 BR BR9916314-4A patent/BR9916314A/pt not_active IP Right Cessation
- 1999-12-16 AR ARP990106461A patent/AR021718A1/es unknown
- 1999-12-16 CN CNB99816206XA patent/CN1326850C/zh not_active Expired - Fee Related
- 1999-12-16 HU HU0202152A patent/HUP0202152A2/hu unknown
- 1999-12-16 TR TR2001/01755T patent/TR200101755T2/xx unknown
- 1999-12-16 EP EP99963980A patent/EP1140902A1/en not_active Withdrawn
- 1999-12-17 PE PE1999001295A patent/PE20001342A1/es not_active Application Discontinuation
2001
- 2001-05-23 ZA ZA200104233A patent/ZA200104233B/en unknown
- 2001-06-15 NO NO20012961A patent/NO20012961L/no not_active Application Discontinuation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20160134672A (ko) *	2014-03-19	2016-11-23	비아멧 파마슈티컬즈, 인코포레이티드	2-(2,4-디플루오로페닐)-1,1-디플루오로-1-(5-치환된-피리딘-2-일)-3-(1h-테트라졸-1-일)프로판-2-올 및 이의 제조방법

Also Published As

Publication number	Publication date
AR021718A1 (es)	2002-07-31
SK7592001A3 (en)	2002-03-05
AU776558B2 (en)	2004-09-16
AU2030700A (en)	2000-07-12
NO20012961D0 (no)	2001-06-15
ZA200104233B (en)	2002-08-22
EP1140902A1 (en)	2001-10-10
WO2000037459A1 (en)	2000-06-29
CZ20011950A3 (cs)	2001-12-12
CO5160350A1 (es)	2002-05-30
CN1334811A (zh)	2002-02-06
CA2354779A1 (en)	2000-06-29
PE20001342A1 (es)	2000-12-09
TR200101755T2 (tr)	2001-09-21
JP2002533336A (ja)	2002-10-08
NZ511878A (en)	2003-10-31
HUP0202152A2 (en)	2002-10-28
CN1326850C (zh)	2007-07-18
IL143408A0 (en)	2002-04-21
NO20012961L (no)	2001-08-16
PL348293A1 (en)	2002-05-20
BR9916314A (pt)	2001-10-02

Publication	Publication Date	Title
US6372747B1 (en)	2002-04-16	Farnesyl protein transferase inhibitors
US5712280A (en)	1998-01-27	Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5880128A (en)	1999-03-09	Carbonyl piperazinyl and piperidinyl compounds
US6300338B1 (en)	2001-10-09	Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5891872A (en)	1999-04-06	Tricyclic compounds
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2001-06-16	PA0105	International application	Patent event date: 20010616 Patent event code: PA01051R01D Comment text: International Patent Application
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KR20010081116A - 트리사이클릭 파르네실 단백질 트랜스퍼라제 억제제 - Google Patents

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